含氟和氯的新型生物活性玻璃在抗敏修复牙膏应用的研究

Dentin Hypersensitivity (DH) is a common oral disease that affects up to 35% of the international population. It arises from the exposure of underlying dentine to the oral environment. 45S5 bioactive glass-based toothpastes have been designed and used for treating DH. The incorporated glass particles dissolve after tooth brushing and promote hydroxyapatite (HAP) formation on the tooth surface, therefore occlude the exposed dentin tubules and relieve the pain. However, 45S5 bioactive glass has some disadvantages, including uncontrollable glass degradation rate, high hardness / excess tooth lost, slow HAP formation rate etc. Moreover, the formed hydroxyapatite is not stable in acid condition. .Fluoride has been introduced into bioactive glasses (BG) to inhibit enamel and dentine demineralisation and facilitate the formation of a more acid resistant fluorapatite. However, excess fluoride can also be problematic. As an alternative, chloride has recently been incorporated to sodium free BG which resulted in a reduction of glass hardness and a promotion of glass degradation. The objective of this project are to investigate the possibility of incorporating both small amount of fluoride and various chloride content into Q2 type glasses; investigate their effects on the glass structure, properties and bioactivity; evaluate the effects of mixed fluoride and chloride containing BG-conditioned medium and BG on cell behaviour. Based on the research results, the optimised glass composition will be finalised and formulated into toothpaste to evaluate its remineralisation ability and dentin tubule occlusion. This project provides the basis for the industrialization of the developed toothpaste and its clinical applications.

牙本质过敏症是一种常见的口腔疾病，世界范围内高达35%的人患有不同程度的此类症状。生物活性玻璃45S5能在唾液中降解，释放离子，在牙齿表面形成羟基磷灰石再矿化层，封闭暴露的牙本质小管，缓解过敏，因此被用做抗敏牙膏的添加剂。然而，由于该玻璃自身的局限性（例如，硬度大、生成羟基磷灰石速度慢、生成的磷灰石在口腔酸性条件下易溶解等），其应用效果并不理想。.研究发现在玻璃中添加氟可以促进生成耐酸的氟磷灰石；添加氯可以扩张玻璃结构，促进玻璃快速降解，降低玻璃硬度从而降低不必要的牙磨损。本项目研究同时含有氟和氯的生物活性玻璃，以期其能成为速效脱敏，高效抗敏和持久保护牙齿的牙膏的添加剂。通过研究玻璃结构、理化性质和体外生物活性，探索玻璃对牙釉质脱矿化和再矿化的影响，分析玻璃对细胞的作用，筛选出最优玻璃组分。最后实验室制备含有该组分的牙膏并研究其对牙本质小管的封闭作用，为研究成果产业化及临床应用提供基础。

牙本质过敏症降低了全球超过35%人口的生活质量。使用具有抗敏功效的牙膏是当前缓解牙本质敏感的首选方式，欧美国家的抗敏技术占据了抗敏牙膏的主要市场。然而，当前仍缺乏能够速效脱敏，高效抗敏和持久保护牙齿的理想脱敏方法。针对该问题，本项目设计并成功合成了一系列同时含有氟化钙和氯化钙的生物活性玻璃，探究了玻璃作为抗敏牙膏添加剂的可行性，并在细胞水平探究了含氟化钙和氯化钙系列生物活性玻璃的生物安全性及其成骨功效。实验结果显示通过将卤化物添加入Q2型硅酸盐玻璃中的方式，能将大量的氯和氟同时保留在硅酸盐玻璃基质中，所获得的玻璃同时结合了氟抑制脱矿、促进再矿化生成耐酸的氟磷灰石生成、加速成骨和氯提高玻璃生物活性，降低玻璃硬度和研磨力等优点。细胞实验结果表明含氟化钙和氯化钙生物活性玻璃无细胞毒性且具有良好的生物安全性，在玻璃中添加适量的氟可以促进矿化结节和胶原生成，上调成骨相关基因的表达，玻璃中的氯化钙能促进细胞增殖，提高细胞的碱性磷酸酶活性，促进成骨细胞矿化结节的形成、成骨基因及蛋白表达上调。体外生物活性研究发现含少量氟化钙和氯化钙的生物活性玻璃在人工唾液中浸泡1小时内能大量生成耐酸的氟磷灰石，同时随着玻璃中氯化钙含量的增加，玻璃或含生物活性玻璃牙膏封闭牙本质小管的效果逐渐提高，其中GPF2.3Cl20和GPF2.3Cl30牙膏的封闭效果最佳，可作为较理想的抗敏牙膏添加剂，为后续产业化转化提供了实验支撑。